Type 1 and 2 of the human immunodeficiency viruses (HIV) are recognized as the etiologic agents for acquired immunodeficiency syndrome (AIDS). A vaccine against these viruses would be an ideal way of preventing infection with HIV and AIDS. Accordingly, much research has been focused on molecular biological analyses of structures and functions of HIV. The main virion structural proteins of HIV are derived from three structural genes known as gag, pol, and env. The genome of many different isolates of HIV have been completely sequenced, and amino acid sequences have been deduced from the cloned proviral DNA sequences. The envelope gene of HIV codes for a glycoprotein precursor with a molecular weight of 160,000 (gp160). The precursor gp160 in virus-infected cells is processed (or cleaved) to produce envelope glycoprotein gp120 and gp41. The envelope glycoproteins gp120 of HIV has been the major target for developing a candidate vaccine against AIDS. gp120 recognizes the cellular receptor (CD4) on helper T lymphocytes, and carries the V3 loop domain that induces neutralizing antibodies (Putney et al., Science 234, 1392-1395 (1986); Robey et al., Proc. Natl. Acad. Science, USA 83, 7023-7027 (1986)).
The V3 loop represents the third hypervariable region of HIV-1 gp120 (amino acid residues 308-331) which contains not only a major immunodominant neutralizing epitope but also the epitopes for antigen-dependent cellular cytotoxicity (ADCC) and cytotoxic T-lymphocyte (CTL) recognition. Although the majority of the amino acids in the V3 loop are variable among different strains of HIV, a G-P-G-R motif at the tip of the loop is conserved (LaRosa et al., Science 249, 932-935 (1990)).
Recently, Huang et al. and Bjorling et al. demonstrated that the principal neutralization domain of the envelope glycoprotein of HIV-2 is also located in the region corresponding to the hypervariable motif in the V3 loop of HIV-1 gp120 (Huang et al., J. Virol. 65,5073-5079 (1991); Bjorling et al., Proc. Natl. Acad. Sci. USA 88, 6082-6086 (1991). The CD4-binding region, located within C-terminal third of HIV-1 gp120 (amino acid residues 397-439), plays an essential role in the infectivity of HIV. This region also seems to be weakly immunogenic because it forms a pocket which is not accessible to the immune system, and, therefore, high-titre neutralizing antibody against this region is not presently available.